The Human T-Cell Leukemia Virus Type I (HTLV-I) X Region Encoded Protein p13II Interacts with Cellular Proteins

Hou, Xiaohong; Foley, Shanon; Cueto, Maria; Robinson, Mary Ann

doi:10.1006/viro.2000.0604

Cited by 14 publications

(12 citation statements)

References 36 publications

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“…Whether this form represents a bona fide p13 II -p13 II dimer, a complex with other proteins, or rather, results from natural post-translational modifications of p13 II or chemical modifications arising during mitochondrial isolation is under investigation. In this connection it is worth mentioning that interactions between p13 II and cellular proteins have been described in a yeast 2-hybrid screen (33). This analysis identified two binding partners for p13 II coded by the K34 molecular clone, C44, a protein that shows substantial similarities to archaeal adenylate kinases, and C254, a protein that probably corresponds to non-muscle filamin.…”

Section: Htlv-1 P13 II Function 34431mentioning

confidence: 86%

Mitochondrial Alterations Induced by the p13II Protein of Human T-cell Leukemia Virus Type 1

D’Agostino

Ranzato

Arrigoni

et al. 2002

Journal of Biological Chemistry

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Human T-cell leukemia virus type 1 encodes a number of "accessory" proteins of unclear function; one of these proteins, p13 II , is targeted to mitochondria and disrupts mitochondrial morphology. The present study was undertaken to unravel the function of p13 II through (i) determination of its submitochondrial localization and sequences required to alter mitochondrial morphology and (ii) an assessment of the biophysical and biological properties of synthetic peptides spanning residues 9 -41 (p13 9 -41 ), which include the amphipathic mitochondrialtargeting sequence of the protein. p13 9 -41 folded into an ␣ helix in micellar environments. Fractionation and immunogold labeling indicated that full-length p13 II accumulates in the inner mitochondrial membrane. p13 9 -41 induced energy-dependent swelling of isolated mitochondria by increasing inner membrane permeability to small cations (Na ؉ , K ؉ ) and released Ca 2؉ from Ca 2؉ -preloaded mitochondria. These effects as well as the ability of full-length p13 II to alter mitochondrial morphology in cells required the presence of four arginines, forming the charged face of the targeting signal. The mitochondrial effects of p13 9 -41 were insensitive to cyclosporin A, suggesting that full-length p13 II might alter mitochondrial permeability through a permeability transition pore-independent mechanism, thus distinguishing it from the mitochondrial proteins Vpr and X of human immunodeficiency virus type 1 and hepatitis B virus, respectively.HTLV-1 1 is a complex retrovirus that is associated with two distinct pathologies, a leukemia/lymphoma of mature CD4 ϩ

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Section: Htlv-1 P13 II Function 34431mentioning

confidence: 86%

Mitochondrial Alterations Induced by the p13II Protein of Human T-cell Leukemia Virus Type 1

D’Agostino

Ranzato

Arrigoni

et al. 2002

Journal of Biological Chemistry

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“…During viral infection, p12 I may function by facilitating escape from immune surveillance activity, leading to unchallenged clonal expansion of infected T cells in the PB and CNS, and a subsequent overall increase in proviral DNA load. p13 II , an 87 amino acid protein, has been shown to primarily localize to the mitochondria and interact with several cellular proteins (Hou et al, 2000) (Fig. 2).…”

Section: Viral Mechanisms Regulating Htlv-i Infection In Target Cellsmentioning

confidence: 99%

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

Grant

Barmak

Alefantis

et al. 2002

Journal Cellular Physiology

101

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Human T cell lymphotropic/leukemia virus type I (HTLV‐I) has been identified as the causative agent of both adult T cell leukemia (ATL) and HTLV‐I‐associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the exact sequence of events that occur during the early stages of infection are not known in detail, the initial route of infection may predetermine, along with host, environmental, and viral factors, the subset of target cells and/or the primary immune response encountered by HTLV‐I, and whether an HTLV‐I‐infected individual will remain asymptomatic, develop ATL, or progress to the neuroinflammatory disease, HAM/TSP. Although a large number of studies have indicated that CD4+ T cells represent an important target for HTLV‐I infection in the peripheral blood (PB), additional evidence has accumulated over the past several years demonstrating that HTLV‐I can infect several additional cellular compartments in vivo, including CD8+ T lymphocytes, PB monocytes, dendritic cells, B lymphocytes, and resident central nervous system (CNS) astrocytes. More importantly, extensive latent viral infection of the bone marrow, including cells likely to be hematopoietic progenitor cells, has been observed in individuals with HAM/TSP as well as some asymptomatic carriers, but to a much lesser extent in individuals with ATL. Furthermore, HTLV‐I+ CD34+ hematopoietic progenitor cells can maintain the intact proviral genome and initiate viral gene expression during the differentiation process. Introduction of HTLV‐I‐infected bone marrow progenitor cells into the PB, followed by genomic activation and low level viral gene expression may lead to an increase in proviral DNA load in the PB, resulting in a progressive state of immune dysregulation including the generation of a detrimental cytotoxic Tax‐specific CD8+ T cell population, anti‐HTLV‐I antibodies, and neurotoxic cytokines involved in disruption of myelin‐producing cells and neuronal degradation characteristic of HAM/TSP. J. Cell. Physiol. 190: 133–159, 2002. © 2002 Wiley‐Liss, Inc.

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“…Thus far, it has not been demonstrated that p13 nylate kinases, the eukaryotic homologues of which localize to mitochondria. Interestingly, the human homologue of C44 is expressed in the Jurkat T-cell line and proliferating, but not resting, PBMC (57). The implications of this finding remain unclear but allow speculation about a potential role of p13 II in cellular activation.…”

Section: Mitochondria: Target Of Px Orf II P13 Iimentioning

confidence: 99%

Critical Role of Human T-Lymphotropic Virus Type 1 Accessory Proteins in Viral Replication and Pathogenesis

Albrecht¹,

Lairmore

2002

Microbiol Mol Biol Rev

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Human T-cell lymphotropic virus type 1 (HTLV-1) infection is associated with a diverse range of lymphoproliferative and neurodegenerative diseases, yet pathogenic mechanisms induced by the virus remain obscure. This complex retrovirus contains typical structural and enzymatic genes but also unique regulatory and accessory genes in four open reading frames (ORFs) of the pX region of the viral genome (pX ORFs I to IV). The regulatory proteins encoded by pX ORFs III and IV, Tax and Rex, respectively, have been extensively characterized. In contrast the contribution of the four accessory proteins p12I, p27I, p13II, and p30II, encoded by pX ORFs I and II, to viral replication and pathogenesis remained unclear. Proviral clones that are mutated in either pX ORF I or II, while fully competent in cell culture, are severely limited in their replicative capacity in a rabbit model. Emerging evidence indicates that the HTLV-1 accessory proteins are critical for establishment of viral infectivity, enhance T-lymphocyte activation, and potentially alter gene transcription and mitochondrial function. HTLV-1 pX ORF I expression is critical to the viral infectivity in resting primary lymphocytes, suggesting a role for p12I in lymphocyte activation. The endoplasmic reticulum and cis-Golgi localizing p12I, encoded from pX ORF I, activates NFAT, a key T-cell transcription factor, through calcium-mediated signaling pathways and may lower the threshold of lymphocyte activation via the JAK/STAT pathway. In contrast p30II localizes to the nucleus and represses viral promoter activity, but may regulate cellular gene expression through p300/CBP or related coactivators of transcription. p13II targets mitochondrial proteins, where it alters the organelle morphology and may influence energy metabolism. Collectively, studies of the molecular functions of the HTLV-1 accessory proteins provide insight into strategies used by retroviruses that are associated with lymphoproliferative diseases

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The Human T-Cell Leukemia Virus Type I (HTLV-I) X Region Encoded Protein p13II Interacts with Cellular Proteins

Cited by 14 publications

References 36 publications

Mitochondrial Alterations Induced by the p13II Protein of Human T-cell Leukemia Virus Type 1

Mitochondrial Alterations Induced by the p13II Protein of Human T-cell Leukemia Virus Type 1

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

Critical Role of Human T-Lymphotropic Virus Type 1 Accessory Proteins in Viral Replication and Pathogenesis

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